Data collected in our laboratory and others have shown that the BHE strain of rat may serve as an excellent animal model for the study of maturity onset diabetes and lipemia. It has been demonstrated that the diet, particularly high sugar (sucrose or glucose) diets can enhance the genetic tendency of this rat strain towards excess hepatic lipogenesis without affecting body weight gain. This proposal is designed to study characteristics of the BHE strain and the diet-genetic interaction in the regulation of hepatic lipogenesis as compared to adipocyte lipogenesis. Hepatic lipogenic capacity as a function of the influence of diet, age, hormonal status and genetic background will be studied in detail, focusing on the possible differences in metabolic control which might explain the age related development of lipemia and hyperglycemia. Gluconeogenesis, glycolysis and lipogenesis in isolated hepatocytes and adipocytes will be studied as will isolated mitochondria from these tissues. Mitochondrial respiration, shuttle activities, adenine nucleotide translocase activities as well as anion/cation exchanges will be studied as needed and where applicable. Different diets, drugs and antimetabolites will be used in control rats in an attempt to reproduce the metabolic states observed in the BHE rats so as to provide or disprove the role of any one cellular characteristic in the genesis of maturity onset diabetes and lipemia. Methods for each of the above studies are already operational in our laboratories. Experimental animals are readily available from our own colony of BHE rats, inbred for 14 generations with selection pressure placed on the hyperlipemic/hyperglycemic characteristic. Overall, the studies proposed here will provide a clearer understanding of the role of diet and inheritance in the development of maturity onset diabetes and lipemia. In addition, it may provide the technology for identifying potential diabetics before their disease becomes manifest thereby allowing prophylactic therapy to be instituted lenghtening that individual's productive lifespan.